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Administrative data

Description of key information

Oral route: Approximate LD50 of 2,000 mg/kg estimated (OECD 401).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 March 1990 - 20 April 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study protocol was not in accordance with modern guidelines, which for example would have required fewer animals, but the scientific basis of the method followed is nevertheless robust
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(animals were not observed 30 minutes after dosing)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CDBr (Sprague-Dawley)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Kingston Facility, Stone Ridge, New York.
- Age at study initiation: Males, approximately 8 weeks old; females, approximately 11 weeks old.
- Weight at study initiation: Males 230–243 g; females 203–211 g.
- Fasting period before study: Food witheld overnight prior to dosing.
- Housing: Individual, except during the first week of acclimation. Suspended stainless steel cages.
- Diet (e.g. ad libitum): Ad libitum.
- Water (e.g. ad libitum): Ad libitum.
- Acclimation period: 7 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68-76 ºF (20-24.4ºC).
- Humidity (%): 30-70%.
- Air changes (per hr): Not stated.
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark.


IN-LIFE DATES: From: 22 March 1990 To: 05 April 1990.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.96 mL/kg.
Doses:
2000 mg/kg
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations : Animals were observed for viability and signs of toxicity at 1, 2, 4 and 6 hours after dosing and at least daily thereafter.
- Frequency of weighing: Individual bodyweights were recorded prior to dosing, at initiation of dosing (Day 0), and at Day 7 and Day 14 (or at death for animals dying during the study).
- Necropsy of survivors performed: Yes.
Statistics:
The mean and standard deviations of the body weights and body weight changes were calculated.
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
2 000 mg/kg bw
Remarks on result:
other: Estimated LD50
Mortality:
Five (2 male and 3 female) animals died on the day of dosing (Day 0). The remaining five animals survived to termination.
Clinical signs:
In-life signs of toxicity most frequently observed included: tremors; oral, nasal and ocular discharge; staining of the anogenital and abdominal areas. Other signs included hypoactivity, hypothermia, abnormal stool production, hyperactivity, convulsions and rales. Surviving animals showed no signs of toxicity from Day 7 onwards.
Body weight:
The five animals that survived until study termination showed an increase in body weight over the initial values.
Gross pathology:
Gross pathology of animals that died during the study included abnormalities of the gastrointestinal tract, liver and lungs. Single incidences of undescended testes and an abnormal white mass within the urinary bladder were also noted. No gross pathology was found in surviving animals.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Five of the ten animals died on the day of dosing. Necropsy of these animals revealed abnormalities of the gastrointestinal tract, liver and lungs. Single incidences of undescended testes and an abnormal white mass within the urinary bladder were also noted. The five remaining animals survived until study termination and displayed no gross pathology at necropsy. Based on the five deaths, an approximate LD50 of 2,000 mg/kg may be estimated.
Executive summary:

The test material was assessed for acute oral toxicity potential in a GLP study (limit test) in Sprague-Dawley rats. Five males and five females were administered the neat test material by gavage at a dose of 2,000 mg/kg bodyweight and observed for 14 days. Body weights were measured prior to dosing, one week after dosing, and prior to termination. Two males and three females died on the day of dosing. Gross necropsy of these animals revealed abnormalities of the gastrointestinal tract, liver and lungs. Single incidences of undescended testes and an abnormal white mass within the urinary bladder were also noted. The five remaining animals survived until study termination and displayed no gross pathology at necropsy. Based on the five deaths, an approximate LD50 of 2,000 mg/kg may be estimated.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
28 April 1995 - 27 July 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in accordance with OECD guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CDBR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Inc., Kingston Facility, Stoneridge, New York.
- Age at study initiation: Males were approximately 7 weeks old and females approximately 8 weeks old at initiation of dosing.
- Weight at study initiation: Males were 209-218 grams and females 183-194 grams at initiation of dosing.
- Fasting period before study: animals were fasted from approximately 4:00pm on the day prior to dosing until completion of dosing the following morning.
- Housing: Single housed during the study period.
- Diet (e.g. ad libitum): ad libitum, apart from fasting period prior to and following dosing.
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68-76 ºF (approx 20-24.5ºC)
- Humidity (%): 40-70%
- Air changes (per hr): Not stated.
- Photoperiod (hrs dark / hrs light): 12 hours light (07:00-19:00 hours) and 12 hours dark (19:00-07:00 hours)

IN-LIFE DATES: From: 02 May 1995 To: 16 May 1995.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
The test material was administered at a single dose of 2,000 mg/kg bw.
No. of animals per sex per dose:
5 males and 5 females.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.

- Frequency of observations and weighing: Animals were observed for viability twice daily Monday through Friday, and once daily at weekends. Clinical observations were made as to the nature, onset, severity, and duration of toxicological signs at 1, 2, 4, and 6 hours after dosing, and once per day thereafter for a total of 14 days. Bodyweights were recorded on the day prior to dosing (pretest), the day of dosing (Day 0), on Day 7, and on Day 14.

- Necropsy of survivors performed: Yes.
Statistics:
Statistical analyses included means and standard deviations of body weight and body weight change by group and sex.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths; all animals survived to scheduled sacrifice.
Clinical signs:
Clinical signs were limited to four animals. The majority of the findings consisted of oral or nasal discharge and or anogenital or abdominal staining. One female was also observed with decreased food consumption, slight emaciation, and/or stool abnormalities from Day 3 to Day 8. All animals were free of abnormalities from Day 9 to study termination.
Body weight:
All animals displayed increases in body weight over their initial values. However, one male displayed a weight decrease at the Day 7 weighing interval.
Gross pathology:
No gross abnormalities were seen in any animal at postmortem examination.
Other findings:
No other findings were reported.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No deaths occurred at 2,000 mg/kg bw. The acute oral LD50 of the test material in the rat is therefore greater than 2,000 mg/kg bw.
Executive summary:

The test material was evaluated for acute oral toxicity potential in a GLP study conducted in accordance with OECD Test Guideline 401. The study was conducted as a limit test, in which the test material was administered by gavage to five male and five female Crl:CDBR rats at a single dose of 2,000 mg/kg bw.

All animals survived the 14-day observation period to scheduled termination. Clinical signs were observed in four animals. Principally these consisted of oral or nasal discharge and/or anogenital or abdominal staining, though one female showed decreased food consumption, slight emaciation and/or stool abnormalities from Day 3 to Day 8. One male had a decreased body weight at the Day 7 interval, but all animals gained weight overall. Necropsy revealed no gross abnormalities. The acute oral LD50 of the test material in the rat is concluded to be greater than 2,000 mg/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Between March 9th, 1997 and March 30th, 1977
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study; well-documented study report.
Qualifier:
according to guideline
Guideline:
other: Federal Hazardous Substances Act, Section 1500.41
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sherman
Sex:
male
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
0.63, 1.25, 2.5, 5.0 and 10.0 ml/kg
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male
Dose descriptor:
LD50
Effect level:
> 10 mL/kg bw
Mortality:
No
Clinical signs:
No unusual behavioral signs were noted.
Gross pathology:
Gross pathologic examination revealed nothing remarkable.

All test animals survived the 14-day test period. 

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
LD50 > 10ml/kg, and the test substance is non-toxic within the definition of the Federal Hazardous Substances Act, Section 1500.3
Executive summary:

An acute oral toxicity study was performed using male Sherman-Wistar rats according to the definition of the Federal Hazardous Substances Act, Section 1500.3. Groups of 5 rats weighing 200 -300 g were administered single doses of 0.63, 1.25, 2.5, 5.0 and 10.0  ml/kg test material by oral gavage and observed post-dose for 14 days. Mortality was not observed in all dose groups. No unusual behavioral signs were noted. Gross pathologic examination revealed nothing remarkable. Based on these results the test article is considered to be non-toxic at the concentrations tested.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

This substance does not show any evidence of toxicity via the oral route of exposure in animals when tested in accordance with FHSA 16 CFR 1500.3 (1977). The rat oral LD50 is greater than 10 ml/kg bw. No mortality occurred. No signs of systemic toxicity, or behavioral changes were reported during the study, and no abnormalities were noted at necropsy. In a second study this substance shows evidence of toxicity when tested in accordance with OECD 401. The rat oral LD50 is estimated at approximately 2000 mg/kg. No gross pathology was found in surviving animals. No specific organ toxicity is evident.

 

The dermal route for acute toxicity is appropriate if the physicochemical properties suggest there is potential for a significant rate of absorption through the skin. The scientific literature regarding dermal toxicity states that for those substances with a log Kow greater than 5 there is very limited potential for dermal absorption (e.g,. 10% absorption) (Annals of Occupatinoal Hygiene, 47(8):641-652, 2003). The test material has a Log Kow greater than 7.1 (small portion < 0.3) thereby demonstrating that it has very limited dermal absorption potential. In contrast, oral absorption can be relatively fast due to contact surface areas in the GI tract resulting in a peak concentration in the body, and GI tract has been regarded as the route resulting in higher bioavailability. For the test material, dosing via oral route represents the worst case scenario for assessing acute exposure, and acute dermal toxicity end point satisfied by acute oral toxicity results (LD50>2000 mg/kg).

 

Integrated testing strategies for acute toxicity state that determination of the most likely route of exposure needs to take into account not only how the substance is manufactured and handled, including engineering controls and risk management measures, but also the physicochemical properties of the substance. The test material is intended for use as an antiwear agent for grease, gear oil lubricants and farm tractor lubricants. Gear oils and manual transmission fluids are typically used in fill for life applications therefore down-stream exposure will be low; the application in grease products is predicted to have low exposure potential. Also the test materialhas very low volatility. The vapour pressure has been determined to be 0.032 Pa at 25oC, thus there is minimal potential for any inhalation of gases or vapors. ECHA guidance states that for the inhalation route no testing is required if the vapor pressure is very low (< 0.1 Pa at 20oC) (see ECHA Guidance R.7 as well as OECD GD 39). Therefore inhalative acute toxicity is of no relevance.

Based on a weight of evidence analysis of the manufacturing and handling, physicochemical properties, and available toxicological information, the substance was excluded from the need for acute dermal and inhalation toxicity testing as it is not scientifically necessary, the available information is sufficient for an adequate hazard characterization, and the exposure to the substance is adequately controlled.

Justification for classification or non-classification

In accordance to Directive 67/548/EEC and EU CLP (Regulation (EC) No. 1272/2008), classification of this substance is required for acute toxicity.